INCREASED EPIDERMAL GROWTH-FACTOR RECEPTOR IN AN ESTROGEN-RESPONSIVE,ADRIAMYCIN-RESISTANT MCF-7 CELL-LINE

We examined the expression of the estrogen and epidermal growth factor (EGF) receptors in a drug-resistant subline of MCF-7 cells in order t o study potential alterations in hormone dependence or in the growth f actor pathway that could be related to the development of drug resista nce in human breast cancer. The drug-resistant subline was derived fro m MCF-7 cells by selection with Adriamycin in the presence of the P-gl ycoprotein antagonist, verapamil, to prevent acquisition of the classi cal multidrug resistance phenotype. The Adriamycin-resistant cells ret ain estrogen-binding, estrogen-responsive monolayer growth, and estrog en-dependent tumorigenesis. Estrogen-binding studies demonstrate 1.4 x 10(6) sites per cell with unaltered affinity when compared to parenta l MCF-7 cells, which have 2.7 x 10(5) sites per cell. Ah increase in e xpression of EGF receptor, eight to 12-fold, occurred early in the sel ection for drug resistance, and appears to be unrelated to verapamil e xposure, since cells maintained in Adriamycin without verapamil also h ave increased EGF receptor expression. Partially drug-sensitive revert ants carried a verapamil, but out of Adriamycin, demonstrate a decline in EGF receptor expression. We postulate that activation of growth fa ctor pathways in drug-resistant cells may enhance mechanisms of drug r esistance, or provide mitogenic stimuli for cells to recover after dam age by drug exposure. (C) 1993 Wiley-Liss, Inc.